Bioinformatics – WHY? WHAT? HOW? Computational Thinking / Programming in Bioinformatics 1) Data Sciences 2) Dynamic Programming 3) IT software / tools 4) High Performance Computing (HPC)

1. Computational Thinking
in Bioinformatics
Unleashed
Mujitha Bai K B
WhizThinkers
https://whizthinkers.com

2. The Story….
Gulbarga – prevalence and incidence of structural birth defects is very high
- Mostly due to marriages within relatives / families
- e.g. cleft palate, heart defects, club foot, missing or abnormal limbs

3. The Story….
In a private hospital in Gulbarga, a child is born with cleft palate
Kid’s genome is sequenced for ~Rs. 1 lakh
Kid has a series of diagnostics/treatments
with surgeons, oncologists etc.
Unfortunately, the kid develops cancer at
the age of 9
The birth defect was reported in Kids First Research platform
Free of cost, At a Kids First-supported sequencing center,
specimen was sequenced (WGS, WES, TS)
Gabriella Miller Research approach
Clinical & Phenotype data of kid / parents / siblings submitted
Normal approach
In combination with other data, researchers/clinicians at Kids
First gave upfront consultation on how to prevent cancer
This case made a major breakthrough in nutritional deficiency
(lack of folic acid) related Research on birth defects

4. Bioinformatics – WHY? WHAT? HOW?
Computational Thinking / Programming in Bioinformatics
Data Sciences
Dynamic Programming
IT software / tools
High Performance Computing (HPC)

6. Informatics = data processing, storage and retrieval
Bio + Informatics
Applicable data scales are defined as:
- Genomic (e.g., DNA sequence, epigenetic state)
- Molecular/subcellular (e.g., RNA / protein abundance)
- Cellular (e.g., cell-state, cell-type)
- Tissue (e.g., tissue morphology, metabolic state)
- Individual patient (e.g., clinical data, exposure, microbiome)
- Population (e.g., epidemiological)
Biological level

7. Gabriella Miller Kids First DRC – supported by NIH (National Institutes of Health)
Enables researchers, clinicians, patients to work together to accelerate research
Promotes new discoveries for children affected with cancer and structural birth defects
- Data repositories
- Data processing pipelines
A collaborative, pediatric research effort to understand the genetic causes and links between
childhood cancer and structural birth defects.

8. Improved technologies and genome sequencing efforts have transformed
diagnostic and precision medicine approaches in healthcare
Why such a dedicated Global Research platform?
Childhood cancer and birth defects can be challenging to study due to the
limited amounts of patient samples available in any one institution

9. Bioinformatics - End to End Flow
TCGA – The Cancer Genome Atlas
TARGET - Therapeutically Applicable Research to Generate Effective Treatments
CPTAC - Clinical Proteomic Tumor Analysis Consortium

10. Computational Thinking / Programming
in Bioinformatics
Data Sciences
Dynamic Programming
IT software / tools
High Performance Computing (HPC)

11. Analytics & Data Sciences needs

12. Dynamic Programming
- Mainly an optimization over plain recursion
- Repeated calls for same inputs, optimize it using Dynamic Programming
- The idea is to simply store the results of sub problems, so that we do not have to re-
compute them when needed later
Fibonacci Numbers
https://www.geeksforgeeks.org/dynamic-programming/

13. Dynamic Programming in Bioinformatics
- DNA Sequences – Alignment & Analysis (Global Alignment, Local Alignment)
- Proteins – Alignment, Analysis & Structure
- Finding Hidden Messages in DNA
- Comparing Genes, Proteins, Genomes
- Molecular Evolution
- String Processing, Pattern Matching, Clustering
- Finding Mutations in DNA & Proteins
https://www.edx.org/es/course/dynamic-programming-applications-in-machine-learni
(how dynamic programming and Hidden Markov Models can be
used to compare genetic strings and uncover evolution)
“Computational problem formulation”
- formulating a computational problem from a biological question can prove very difficult;
- it is a rare skill that few have, and you should aim to become a problem formulation expert.

14. Research Tools & IT needs

15. • Aggregate computing power in a way that delivers
- much higher performance than one could get out of a desktop computer
- in order to solve large problems in science, engineering, or business
High Performance Computing (HPC)
• Developing scalable applications using HPC architecture (e.g. on AWS Big data platform)
with parallel and distributed computing algorithms
• Cloud Technologies enabling Multi-Cloud Strategy, Hybrid Cloud, Cloud to Edge, etc.
- Cloud as a Service
- AI-driven Multi-Cloud Operations
• Containers and Microservices
• Serverless Computing

16. High Performance Computing (HPC) for data management & analysis
- in biological research and
- to solve difficult Big Data problems
Data can be
- DNA or amino acid sequences
- Microarray or NGS data
- Images
- Mass spectrometry data
- Text articles, or
- Any other biological information
Discoveries - Biological
Interpretation

17. High Performance Computing (HPC) in Bioinformatics
- Basic architectures and methods for implementing HPC on powerful servers,
clusters and the cloud
- Various multi-threaded applications for sequence search and read alignment,
as well as basic usage of multiple cores simultaneously using OS processes
- Cluster computing using job managers such as SGE, LSF and PBS

18. Structural and functional birth defects
What are Structural Birth Defects and Functional Birth Defects?
Birth defects are either structural or functional abnormalities. Structural birth defects include abnormalities in
the development of body parts including the skeleton and organs. Functional birth defects are abnormalities in
the systems that run the body like the neurological, immune and endocrine systems. Major structural
abnormalities may be identified at birth, but functional abnormalities can take months or years to identify.
Structural Birth Defects
Structural birth defects are abnormalities in the structure of body parts. Examples of structural birth defects
include cleft palate, heart defects, club foot, missing or abnormal limbs, etc. Most structural defects develop in
the earliest weeks of pregnancy when all of the organs and the skeleton are forming. The most common
structural birth defects are heart defects.
Causes of Structural Birth Defects
Structural birth defects can be part of a genetic syndrome (about 20%) or they can be caused by
environmental factors during conception and pregnancy. These factors can include maternal illnesses (ex.
Diabetes or toxoplasmosis); viruses (rubella and CMV); alcohol and/or smoking; nutritional deficiencies (lack of
folic acid); exposures to teratogens (ex. medications, radiation, chemicals, heavy metals.) Most structural birth
defects, however, are multi-factorial. This means that a genetic predisposition for a birth defect is triggered by
an adverse factor or exposure in the maternal or paternal prenatal or pre-conceptual history. (For more on
birth defect causes and prevention, visit our Healthy Baby Resource.)
https://birthdefects.org/structural-and-functional-birth-defects/

19. THANK YOU
WhizThinkers
https://whizthinkers.com